Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism

被引：176

作者：

Zhu, XY ^{[1
]}

Topouzis, S ^{[1
]}

Liang, LF ^{[1
]}

Stotish, RL ^{[1
]}

机构：

[1] MetaMorphix Inc, Savage, MD 20763 USA

来源：

CYTOKINE | 2004年 / 26卷 / 06期

关键词：

myostatin; Smad proteins; TGF-beta;

D O I：

10.1016/j.cyto.2004.03.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

As a member of the TGF-beta superfamily, myostatin is a specific negative regulator of skeletal muscle mass. To identify the downstream components in the myostatin signal transduction pathway, we used a luciferase reporter assay to elucidate myostatin-induced activity. The myostatin-induced transcription requires the participation of regulatory Smads (Smad2/3) and Co-Smads (Smad4). Conversely, inhibitory Smad7, but not Smad6, dramatically reduces the myostatin-induced transcription. This Smad7 inhibition is enhanced by co-expression of Smurf1. We have also shown that Smad7 expression is stimulated by myostatin via the interaction between Smad2, Smad3, Smad4 and the SBE (Smad binding element) in the Smad7 promoter. These results suggest that the myostatin signal transduction pathway is regulated by Smad7 through a negative feedback mechanism. (C) 2004 Elsevier Ltd. All rights reserved.

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页码：262 / 272

页数：11

相关论文

共 44 条

[1]

ARNOLD H, 2001, LIFE XY, V1, P1001

[2] Smads as transcriptional co-modulators [J].

Attisano, L ;

Wrana, JL .

CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (02) :235-243

[3] Efficient TGF-β induction of the Smad7 gene requires cooperation between AP-1, Sp1, and Smad proteins on the mouse Smad7 promoter [J].

Brodin, G ;

Åhgren, A ;

ten Dijke, P ;

Heldin, CH ;

Heuchel, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :29023-29030

[4] Regulation of transforming growth factor beta- and activin-induced transcription by mammalian Mad proteins [J].

Chen, Y ;

Lebrun, JJ ;

Vale, W .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (23) :12992-12997

[5] Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene [J].

Dennler, S ;

Itoh, S ;

Vivien, D ;

ten Dijke, P ;

Huet, S ;

Gauthier, JM .

EMBO JOURNAL, 1998, 17 (11) :3091-3100

[6] HUMAN TRANSFORMING GROWTH FACTOR-BETA COMPLEMENTARY-DNA SEQUENCE AND EXPRESSION IN NORMAL AND TRANSFORMED-CELLS [J].

DERYNCK, R ;

JARRETT, JA ;

CHEN, EY ;

EATON, DH ;

BELL, JR ;

ASSOIAN, RK ;

ROBERTS, AB ;

SPORN, MB ;

GOEDDEL, DV .

NATURE, 1985, 316 (6030) :701-705

[7] Smads:: Transcriptional activators of TGF-β responses [J].

Derynck, R ;

Zhang, Y ;

Feng, XH .

CELL, 1998, 95 (06) :737-740

[8] Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15Ink4B transcription in response to TGF-β [J].

Feng, XH ;

Lin, X ;

Derynck, R .

EMBO JOURNAL, 2000, 19 (19) :5178-5193

[9] CLONING OF A TGF-BETA TYPE-I RECEPTOR THAT FORMS A HETEROMERIC COMPLEX WITH THE TGF-BETA TYPE-II RECEPTOR [J].

FRANZEN, P ;

TENDIJKE, P ;

ICHIJO, H ;

YAMASHITA, H ;

SCHULZ, P ;

HELDIN, CH ;

MIYAZONO, K .

CELL, 1993, 75 (04) :681-692

[10] A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle [J].

Grobet, L ;

Martin, LJR ;

Poncelet, D ;

Pirottin, D ;

Brouwers, B ;

Riquet, J ;

Schoeberlein, A ;

Dunner, S ;

Menissier, F ;

Massabanda, J ;

Fries, R ;

Hanset, R ;

Georges, M .

NATURE GENETICS, 1997, 17 (01) :71-74

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